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2015-10-19

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cc-by (c) Moncunill-Massaguer,Cristina et al., 2015
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/96766

A novel prohibitin-binding compound induces the mitochondrial apoptotic pathway through NOXA and BIM upregulation

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Recurs relacionat

http://dx.doi.org/10.18632/oncotarget.6154

Resum

We previously described diaryl trifluorothiazoline compound 1a (hereafter referred to as fluorizoline) as a first-in-class small molecule that induces p53-independent apoptosis in a wide range of tumor cell lines. Fluorizoline directly binds to prohibitin 1 and 2 (PHBs), two proteins involved in the regulation of several cellular processes, including apoptosis. Here we demonstrate that fluorizoline-induced apoptosis is mediated by PHBs, as cells depleted of these proteins are highly resistant to fluorizoline treatment. In addition, BAX and BAK are necessary for fluorizoline-induced cytotoxic effects, thereby proving that apoptosis occurs through the intrinsic pathway. Expression analysis revealed that fluorizoline induced the upregulation of Noxa and Bim mRNA levels, which was not observed in PHB-depleted MEFs. Finally, Noxa-/-/Bim-/- MEFs and NOXA-downregulated HeLa cells were resistant to fluorizoline-induced apoptosis. All together, these findings show that fluorizoline requires PHBs to execute the mitochondrial apoptotic pathway.

Matèries

Càncer, Apoptosi, Mitocondris

Matèries (anglès)

Cancer, Apoptosis, Mitochondria

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Col·leccions

Articles publicats en revistes (Farmacologia, Toxicologia i Química Terapèutica)
<b>Publicacions de projectes de recerca finançats per la UE</b>
Articles publicats en revistes (Ciències Fisiològiques)
Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))
Articles publicats en revistes (Química Inorgànica i Orgànica)

Citació

MONCUNILL MASSAGUER, Cristina, SAURA-ESTELLER, José, PÉREZ-PERARNAU, Alba, PALMERI, Claudia mariela, NÚÑEZ-VÁZQUEZ, Sonia, COSIALLS CASTEL, Ana mª, GONZÁLEZ GIRONÉS, Diana m., POMARES, Helena, KORWITZ, Anne, PRECIADO GALLEGO, Sara, ALBERICIO PALOMERA, Fernando, LAVILLA GRÍFOLS, Rodolfo, PONS I IRAZAZÁBAL, Gabriel, LANGER, Thomas, IGLESIAS I SERRET, Daniel, GIL I SANTANO, Joan. A novel prohibitin-binding compound induces the mitochondrial apoptotic pathway through NOXA and BIM upregulation. _Oncotarget_. 2015. Vol. 6, núm. 39, pàgs. 41750-41765. [consulta: 20 de desembre de 2025]. ISSN: 1949-2553. [Disponible a: https://hdl.handle.net/2445/96766]

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